Rader Lab:

Our main research direction is toward advancing cervical cancer prevention and control. Infection with high-risk human papillomavirus (HPV) is the primary inciting event, but it is evident that additional factors must be involved, since only a small proportion of infected women develop cancer. The laboratory concentrates on identifying genes involved in the progression of cervical cancer through the analysis of molecular changes in preinvasive and invasive neoplasias of the cervix, in addition to identifying host genetic susceptibility polymorphisms in the progression of disease.

Through our work we have found a strong association between the HLA DQB1 locus and invasive cervical cancer in women with high-risk HPV. Using the transmission/disequilibrium test (TDT) test with family based controls we are now identifying additional variations in host and viral DNA that influence vulnerability to cervical cancer.

Through microarray techniques and candidate gene approaches we are dissecting the molecular changes that occur in the progression from preinvasive to invasive cervical disease. Candidate genes on 6p and 11q are being intensively investigated for their role in early carcinogenesis and poor prognosis respectively.

We are also actively involved in translating laboratory work into patient care. Presently we are developing chemoprevention trials to interrupt the progression of viral infection to cervical cancer. Through these ongoing trials we also expect to identify intermediate biomarker endpoints and novel screening markers.

These projects and resources provide a wide range of training opportunities as well as an opportunity to contribute to an import area of research.  See our website for how you can help. 

Mutch/Powell/Goodfellow Lab:

Our laboratory is investigating the genetic alterations that underlie development of uterine endometrial cancers. Endometrial cancer is the most common gynecologic malignancy in the United States. Like many cancers, uterine endometrial cancers are hormonally- responsive tumors. The genetic defects that are associated with the phenotypic progression from normal endometrium to carcinoma are elucidated through direct examination of primary human and mouse tumor tissues and precursor lesions. The lab’s efforts focus on the characterization of how changes in methylation of key regulatory sequences contribute to the cancer state, defining the inherited and acquired causes of defective DNA mismatch repair and determining how loss of DNA mismatch repair contributes to genotypic progression.

Endometrial, colon and other tumors with defective DNA mismatch repair accumulate large numbers of mutations. However, the genes that acquire mutations as a result of loss of mismatch repair remain elusive. We are attempting to determine how defective mismatch influences phenotypic and genotypic progression using a mouse model. Tumors are promoted with the synthetic estrogen, DES, in mice in which the Mlh1 DNA mismatch repair gene has been knocked out. Expression profiling in cancers and precancerous lesions provides candidate genes that are verified in mouse tumors, and their role in disease validated in human cancers.